Project Summary Long Term Goal: To develop a drug for treating inflammatory bowel disease with reduced side effects Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. There are two types of inflammatory bowel disease;Crohn's disease, primarily affecting the small intestine and ulcerative colitis, which affects only the colon. Approximately 1 million people in the U.S. suffer from IBD. Currently used therapeutics are anti-TNF antibodies, which are highly effective in treating both Crohn's disease and ulcerative colitis. However, because they are delivered by injection and neutralize TNF throughout the body, their use is associated with serious side effects, including the reactivation of tuberculosis and a long-term risk of malignancy. Avaxia is developing an oral polyclonal anti-TNF antibody therapeutic for IBD from the early milk (colostrum) of immunized cows. Bovine colostral antibodies are ideal for oral delivery, as the antibodies are stable to gastric digestion and there is a long history of safe human exposure. Published data have established that oral delivery of a polyclonal anti-TNF antibody dramatically reduced colitis in a well-established rodent model of IBD. We hypothesize that oral administration of anti-TNF antibody will enable targeted distribution to the site of inflammation in the gut, with minimal systemic exposure, thus eliminating side effects while maintaining therapeutic efficacy. The goal of the work described in this SBIR phase I application is to evaluate the technical feasibility of treating inflammatory bowel disease with oral anti-TNF bovine colostral antibody. The specific aims are as follows: To test the activity and gastric stability of the anti-TNF antibody in vitro (SA#1). To test the activity of orally administered anti-TNF antibody in mice with TNBS induced colitis (SA#2). To define the distribution of orally administered anti-TNF antibody in mice with TNBS induced colitis (SA#3). If these studies are successful, the SBIR Phase II application will compare oral bovine polyclonal antibody with systemically administered anti-TNF1 monoclonal antibody. Together, these studies will define the commercial opportunity offered by the bovine antibody and will form the basis of the pre-clinical pharmacology package to be used in support of an IND filing. PUBLIC HEALTH RELEVANCE: Project Narrative Avaxia is developing an oral polyclonal anti-TNF antibody therapeutic for inflammatory bowel disease (IBD), from the early milk (colostrum) of immunized cows. We hypothesize that oral administration of anti-TNF antibody will enable targeted distribution to the site of inflammation in the gut, with minimal systemic exposure. This is expected to maintain therapeutic efficacy while eliminating the side effects which restrict the use of anti-TNF antibody for IBD.